Modern treatment methods have led to a major improvement in the survival rate of children with Wilms' tumor. Combined therapy using surgery, radiation therapy, and chemotherapy now cures more than 85% of patients. However, the outlook is poor for those with unfavorable histology, where the 2 year survival is less than 30%; and for those with any histology and metastases at diagnosis (about 50% survival). More effective means of treating these patients must be developed. At the same time, all treatments have their risk and complications, and refinements of therapy for those with a good prognosis are needed so as to achieve maximum survival with the least morbidity. NWTS-3 is built on the first two studies and uses the staging systems developed therefrom. The questions being asked are: (1) Is 10 weeks of AMD and VCR maintenance therapy enough for Stage I? (2) Is RT needed for Stage II? (3) Does 1000 rad suffice for the treatment of Stage III? (4) Will cyclophosphamide be of value for Stage IV and unfavorable histology? (5) What are the late adversities of successful treatment in NWTS patients? (6) Can adriamycin, a cardio-toxin be eliminated from the treatment of favorable histology Stages II and III?